What can the CF registry tell us about rare CFTR-mutations? A Belgian study

E. De WachterEmail author,
M. Thomas,
S. S. Wanyama,
S. Seneca and
A. Malfroot

Orphanet Journal of Rare Diseases201712:142

https://doi.org/10.1186/s13023-017-0694-1

Received: 21 June 2017

Accepted: 10 August 2017

Published: 22 August 2017

Abstract

Background

CFTR2 provides clinical and functional information of the most common CFTR-mutations. Rare mutations (RMs) occur in only a few patients with limited reported clinical data. Their role in CF-disease liability is hardly documented.

Methods

Belgian CF-Registry 2013 data were analyzed to identify CF with at least 1 RM (CF+RM). Clinical data and sweat chloride of CF+RM were compared to CF-controls, carrying 2 class 1 to 3 mutations (CFclassic). Disease severity was compared between both groups. To avoid bias in the comparison, transplanted patients were excluded from each group.

Results

Seventy-seven CF+RM were identified (77/1183 = 6.5%). Sixty-four different RM were detected, of which 21 had not been previously reported. All RMs, corresponding to HGVS (Human Genome Variation Society) nomenclature, were listed in supplementary data.

Seven transplanted CF+RM were excluded for further analysis. CF+RM had higher age at diagnosis [median (IQR)] [3.7 y (0.3–18.3) vs. 0.3y (0.1–2,0) (p < 0.0001)], lower sweat chloride [96 mmol/L (64–107) vs. 104 mmol/L (97–115) (p < 0.0001)], higher FEV1%pred [77%pred (58–96) vs. 68%pred (48–86) (p = 0.017)], were less frequently pancreatic insufficient [56% vs. 98% (p < 0.0001)], Pseudomonas aeruginosa colonized [24% vs. 44% (p = 0.0093)] and needed fewer IV antibiotics [36% vs. 51% (p = 0.041)] than CFclassic. However, a wide spectrum of disease severity was seen amongst CF+RM.

Conclusions

CF-patients with a RM cover 6.5% of the Belgian CF-population. Rare mutations can be found in severely ill patients, but more often in late diagnosed, pancreatic sufficient patients.